Human neonates and infants with protein calorie malnutrition are at high risk for the development of systemic infections resulting from impaired tissue mobilization of phagocytic cells. These investigations will evaluate pathogenic mechanisms that may account for impaired PMN leukocyte and monocyte mobilization in these and other high risk populations. A major emphasis of these studies will be to define functional relationships between cellular adherence and migratory properties, to determine the pathologic role of aberrant cell adhesiveness in phagocytic disorders, and to determine the influences of cytoskeletal components (specifically, microtubules) on cell translocation and adhesive function. Abnormalities of PMN adherence will be compred to cellular aggregation properties in neonates and PCM infants. Additional studies of aggregation promoting properties (C5a activity) of selected neonatal or PCM sera should allow the delineation of pathologic leukocyte aggregation syndromes in clinically infected neonates or PCM infants demonstrating endotoxemia. The pathologic importance of membrane peroxidation in neonatal PMNs will be studied by evaluating the effects of antioxidants of cell migration, adherence and microtubular display in vitro. Chemotactic factor receptor functions will be further evaluated utilizing radiolabelled ligands under conditions of chemotactic deactivation, and following secretory or phagocytic stimulation. Functional requirements of serum complement proteins and/or specific IgG globulin for chemotaxigenesis will be determined by studying the influence of deficiences of complement proteins and/or specific IgG in neonatal or PCM sera. These investigations should provide new information concerning the clinical relevance of in vitro abnormalities of biologic functions of phagocytes, identify clinical risk factors in these and other high risk pediatric hosts, and provide a framework for therapeutic pharmacologic approaches to inflammatory disorders.